Defeating the Lowest Lows

Evidence suggests that insulin users with type 2 or those who use certain diabetes pills have the same risk of severe hypoglycemia as people with type 1.

Self-sufficiency means not needing to rely on other people for survival. Sounds great, in theory, but there are times when everyone needs a hand. Severe hypoglycemia is a medical situation involving extremely low blood glucose that, by definition, requires assistance to treat. Friends, family, coworkers, or even knowledgeable strangers may, at some point, come to the rescue of a person with diabetes whose blood glucose has gone so low that he or she is unable to self-treat. Even one occurrence of this life-threatening complication is one too many, diabetes experts say, yet severe hypoglycemia is far from rare.

A recent study in JAMA Internal Medicine found that each year in the United States, an estimated 100,000 people go to emergency rooms because of hypoglycemia, with a third of them ending up hospitalized. This number is expected to rise as the number of people with diabetes grows. It represents a huge burden on people with diabetes, their families, and the health care system.

Costly Complication

Severe hypoglycemia is expensive in dollars and damaging to quality of life. Treating the complication can be costly even without a trip to the emergency room. “Most episodes of severe hypoglycemia are dealt with at home using glucagon,” an injectable blood glucose–raising medication, says Elizabeth Seaquist, MD, professor of medicine at the University of Minnesota and the American Diabetes Association’s president of medicine and science. “Glucagon is not cheap.” GoodRx, a free online prescription pricing tool, prices glucagon kits in the $200 range.

When glucagon is not available or given promptly or properly, the next stop is often the emergency room. The cost of an emergency room visit can include ambulance fees as well as the emergency room care. The estimated annual cost of U.S. emergency room visits for hypoglycemia is $600 million, says Andrew Geller, MD, a researcher at the Centers for Disease Control and Prevention and lead author of the JAMA Internal Medicine study.

The medical bills pile higher if a trip to the emergency room ends in hospitalization. In 2009, there were 20,839 hypoglycemia-related hospitalizations of people with type 1 diabetes in the United States, according to a research report presented at the American Diabetes Association’s 2013 Scientific Sessions, with a total cost of $1 billion.

“Those are avoidable costs if we can avoid the hypoglycemia,” Seaquist says. Cutting down on severe lows can also save lives. In 2009, there were an estimated 284 hypoglycemia deaths, according to research presented in 2013. Nonfatal cases of severe hypoglycemia may have long-term health ramifications. “We are just beginning to understand how severe hypoglycemia affects health,” says Seaquist. We do know prolonged hypoglycemia is linked to severe cognitive damage. Some evidence suggests that even brief bouts of severe hypoglycemia can increase the risk of heart disease, cognitive deficits, and death, but the data are inconclusive. No one yet knows whether severe hypoglycemia causes these health issues or if people in poor health are more likely to develop severe hypoglycemia.

A clear consequence of hypoglycemia is that severe lows can cause additional severe lows. “The more you get hypoglycemia, the more blunted your response,” says Geller. People with dulled or no hypoglycemia symptoms (hypoglycemia unawareness) may not realize they need to eat or drink something to treat the low until it’s too late and they need help. To maintain the ability to self-treat, Geller says it’s important to keep the body’s response to hypoglycemia sharp by avoiding mild everyday bouts of hypoglycemia as much as possible.

Gauging Risk

Many people with diabetes have mild low blood glucose episodes, but predicting who is at risk for severe hypoglycemia remains a serious challenge. “There are things we used to think we knew, but now we don’t,” says Seaquist. One thing she does know is that “anyone who is on insulin or a sulfonylurea is at risk.” Along with that, evidence suggests that average blood glucose levels, income, and age may put certain people at risk for severe hypoglycemia, in perhaps some unexpected ways.

Average Blood Glucose

It may seem obvious that lower A1Cs (average blood glucose levels over the previous two to three months) would increase the risk for going too low. The Diabetes Control and Complications Trial (DCCT) found the first realevidence that striving for near-normal blood glucose levels (tight control) raises the risk for severe hypoglycemia. The study showed over an average of 6.5 years that two-thirds of participants using multiple daily insulin injections or an insulin pump had one or more episodes of severe hypoglycemia, compared with a third of those with higher blood glucose targets. It found that tight control worked wonderfully well to prevent or reduce serious long-term damage to the eyes, kidneys, and nerves (a follow-up study identified heart health benefits as well)—but also that frequent and dangerous lows came along with those results.

Preventing diabetes complications with tight blood glucose control has become a pillar of diabetes care thanks to the 31-year-old DCCT. Since findings of that study were announced in 1993, the understanding of severe hypoglycemia has continued to evolve.

Recent data indicate that tight control isn’t the whole story; high A1Cs are also linked to severe hypoglycemia. For example, severe lows occurred equally in people with excellent control (A1Cs of 6.5 percent and lower) and those with poor control (A1Cs of 8.5 percent and higher) in a 2013 study of people with type 1 diabetes published in Diabetes Care. Another 2013 study on the same group of people in The Journal of Clinical Endocrinology & Metabolism suggests that those with an A1C between 7 and 7.5 percent had the lowest risk for severe hypoglycemia.

The evidence that middle-ground A1Cs are protective against severe hypoglycemia isn’t limited to type 1 diabetes. A recent study found that people with type 2 diabetes had a greater risk for severe hypoglycemia when their A1Cs were either near normal (below 6 percent) or indicative of very poor control (above 8.9 percent). The link between severe hypoglycemia and high A1Cs in type 2 diabetes is a topic of continued research.

Income

Evidence suggests that uncontrolled blood glucose levels—and severe hypoglycemia—are more common among people with lower incomes than in those who make more money. A 2014 study in Health Affairs found that low-income people with diabetes were more likely to be hospitalized for hypoglycemia at the end of the month—when money for food may run out before the next paycheck. Too little food plus diabetes medication is a dangerous combination that can lead to severe hypoglycemia.

Age

Geller found that older people are at the highest risk for going low. “Every year, one in 49 insulin-treated seniors visits the emergency room for hypoglycemia,” says Geller. For people over 80, the risk skyrockets: One in eight can expect to go to the emergency room each year for a low.

The reason that the risk of lows increases with age is likely caused by many factors. Dementia and faltering memory can make taking medication properly or eating a challenge, as can eye problems. Poor vision may have contributed to the second most common cause of severe hypoglycemia observed in Geller’s study: mixing up insulin products. Taking rapid-acting insulin when intending to take long-acting insulin, or vice versa, can trigger a low.

Hypoglycemia may be preventable by fine-tuning A1C targets. Individualizing blood glucose goals to minimize the risk of long-term damage to the heart, kidneys, eyes, and nerves and the danger of hypoglycemia has become the foundation of the American Diabetes Association’s treatment guidelines in recent years. “With the new guidelines, it will be interesting to see if there is a reduction in severe hypoglycemia,” says Geller.

If you’re worried about lows, talk to your doctor about your blood glucose targets for before and after meals, possibly at bedtime, and your A1C. Balancing the risk of lows against the prevention of diabetes-related damage to the organs isn’t easy, but remember, you don’t have to do it alone.